Haloacetylenic amines



United States Patent O 3,172,912 HALOACETYLENIC AMINES Nelson R. Easton and Charles W. Ryan, Indianapolis, Ind., assignors to Eli Lilly and Company, Indianapolis, ind, a corporation of Indiana No Drawing. Filed Nov. 28, 1961, Ser. No. 155,451 7 Qlaims. (61. 269-563) This invention relates to a group of novel halogenated acetylenic amines.

The compounds provided by this invention can be represented by the following formula wherein R and R when taken separately, can be hydrogen, C -C alkyl, C C alkenyl, lower alkoxy-substituted C C alkyl, lower alkoxy substituted C C alkenyl, cycloalkyl, cycloalkenyl, aryl, and substituted aryl, and when taken together with the carbon atoms to which they are attached, can be cycloalkyl, cycloalkenyl, polycyclic aryl, and partially hydrogenated polycyclic aryl; R and R when taken separately, can be hydrogen, C C alkyl, C C alkenyl, cycloalkyl, cycloalkenyl, aryl, substituted aryl and aralkyl, and when taken together with the nitrogen atom to which they are attached, can be morpholino, thiornorpholino, piperidino, pyrrolidino and 4-alkylpiperazino; and Hal is a halogen atom of atomic number greater than 10 such as chlorine, iodine, or bromine. Acid addition salts of the free bases represented by the above formula are also included within the scope of this invention.

When R, R R and R are C -C alkyl radicals, they can be illustratively methyl, ethyl, isopropyl, n-butyl, n amyl, 3-methylpentyl, Z-ethylhexyl, n-decyl, sec-hexyl, isooctyl, 4-ethyloctyl, 6-ethyldecyl, undecyl, 2,3,3-trimethylpentyl, neopentyl and the like; and when they represent C C alkenyl radicals, they can be illustratively allyl, methallyl, crotyl, and the like. Lower alkoXy-substit-uted C C alkyl radicals or lower alkoxy substituted C C alkenyl radicals, which R and R can represent are in general, formed by substituting any of the C -C alkyl or C -C alkenyl radicals illustrated above with an alkoxy group. Illustrative radicals thus formed include methoXyallyl, ethoxyethyl, methoxypropyl, isopropoxydecyl, S-butoxy-Z-pentenyl and the like.

When R, R R and R are aromatic radicals, they can be illustratively phenyl, thienyl, furyl, pyridyl, naphthyl and the like, and permissible substituents in these aromatic rings include halogen, C C alkyl, C alkenyl, nitro, perhaloalkyl, acetarnido, alkoxy, di-alkylamino, and the like. Illustrative substituted aromatic radicals which R, R R and R represent thus include a-bromonaphthyl, Z-chlorophenyl, Z-hydroxyfuryl, indenyl, 2 dimethylaminopyridyl, bromothienyl, tolyl, xylyl, allylphenyl, styryl, trifluoromethylphenyl, pentafluoro-ethylphenyl, trichloromethylphenyl, p-(n-heXyDphenyl, S-ethyl-S-acetylaminopyridyl, nitrothienyl, 3-rnethylfuryl, anisyl, ethoxyphenyl, methoxyfuryl, 3-n-butylphenyl, etc.

The term aromatic is used herein in its conventional sense and includes all radicals having aromatic character. (See for example Chapter 3 of Organic Chemistry, Henry Gilman, editor, 2d edition, John Wiley and Sons, New York, 1943.)

R, R R and R when they repreesnt cycloalkyl radicals or cycloalkenyl radicals, can be illustratively cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclo-octyl, methylcyclopentyl, cyclobutenyl, bicyclo[2.2.l]heptyl, cy-

clopentenyl, cyclohexenyl, and the like.

3,1?2,9l2 Patented Mar. 9, 1965 The groups R and R when taken together with the carbon atom to which they are attached, represent cycloalkyl, cycloalkenyl, polycyclic aryl, and partially hydrogenated polycyclic aryl groups, such as, for example, tetralinyl, indanyl, indenyl, fluorenyl, cyclopentenyl, cyclobutyl, dihydroanthranyl, Xanthyl, Xanthenyl, thioxanthyl, dibenzocycloheptadienyl, dibenzocycloheptatrienyl, cycloheptyl, cyclopentyl, methylcyclopentenyl, cyclohexyl, cycloheptenyl, and the like.

When R and R represent aralkyl radicals, they can be, illustratively, benzyl, phenethyl, 2-phenylpropy1, 1- henylethyl, l-tolylethyl, m-chlorobenzyl, p-anisylrnethyl, homoveratryl and the like, the permissible aryl radicals substituted in the alkyl chain being in general those defined above for R, R R and R Representative compounds provided by this invention include the following:

1-chloro-3-methylamino-3-(o-chlorophenyl) -1-pentadecyne 1-chloro-3-dodecylarnino-3 (Z-bromothienyl -5-methyll-octyne N-ethyl-N- Z-ethoxy ethyll-chloro-3-amino-3-pdimethylaminophenylhex-S-enl-yne N-Z-pyridyl-N-methyll-chloro-3-amino-3-a-naphthyll-decyne l-piperidino- 1- (chloro-ethynyl indane 1-bromo-3-a-pipecolino-3-p-anisyl-4,4-dimethyl-1- pentyne 1-chloro-3- (4-indenylamino) -3-(o-al1yloxyphenyl) lnonyne 5-homoveratrylamino-5- ('chloro-ethynyl xanthene 5- l-chlorophenethylamino) -5- (chloro-ethynyl) l-thioxanthene l-iodo-3-t-butylarnino-3-rnethyl l -butyne 1-bro1no-3 -methylarnino-3-n1ethyll-butyne 1-brorno-3-ethylamino-3-methyl-l-butyne .l-chloro-3 -n-butylamino-3-rnethyl-l-butyne 1-cl1loro-3-morpholino-3-methyl- 1 -butyne 1-bromo-3-piperidino-3-methyl-l-butyne N-rnethyl-N-phenyl-l-chloro-3-amino-3-methyl- 1- butyne 1-chloro-3 -p-anisidino-3 -methyl-1-butyne l-bromo-3-ethylamino-3-methyll-pentyne 1-iodo-3 -isopropylamino-3-methyll-pentyne 1-chloro-3-diethylamino-3-rnethyll-pentyne 1-bromo-3 -anilino-3 -methyl-1-pentyne 1chloro-3-ethylamino-3-ethyll-pentyne 1-chloro-3-anilino-3-ethyll-pentyne 1-etl1yiamino-l-(chloro-ethynyl)cyclohexanc l-anilinol-bromoethynylcyclopentane 1-chloro-3-o-aminoanilino-3-methyll-octyne 1-chloro-3 -o-chloranilino-3-methyll-decyne 1-chloro-3 -m-chloranilino-3-rnethyll-nonyne 1-bromo-3-p-toluidino-3-rnethyl l-heptyne 1-chloro-3-m-nitroanilino-3-methyll-hexyne 1-brorno-3-amino-l-butyne,1-bromo-3-methylaminopropyne l-chloro-3-p-chloranilino-3-rnethyll-butyne N-rnethyl-N- Z-methoxyethyl) -3-amino-3 -methyl- 1- pentyne 1-chloro-3 (2,4-dichloranilino) -3,4-dimethyl-1-pentyne 1-bromo-3- (o-brornanilino -3 ,4,4-trimethyl-1-pentyne N-ethyl-N- 3 ,4-dimethoxyphenyl) l-chloro-3-amino- 3 -rnethy1-1-butyne 1-chloro-3 -rn-ethoxyanilino-3-methyll apentadecyne 1-chloro-3-p-toluidino-3-methyll-pentyne l-bromo-3 -p-acetylamino-anilino-3,5 -dimet l1yll-hexyne 1-chloro-3 -p-trifiuoromethylanilino-3 ,4-dimethyllhexyne 1- p-ethylamino -anilino- 1- (chloro-ethynyl) cyclobutane l-(p-butyenylamino)-anilino-1-(bromo-ethynyl) -3 cyclopentene 1- (4-chlorobenzylamino -lchloro-ethynyl cyclohexane 1- (4-pyrrolidino -anilino- 1- (chloro-ethynyl) cycloheptane 1-bromo-3-p-hydroxyanilino-3 -ethyl-1-hexyne Nmethyl-3- 3,4-dimethylanilino -1-chloro-3 -methyll-butyne 1-bromo-3-p-tolyl-3-benzylamino-l-bu'tyne 1-chloro-3-p-chlorophenyl-3-ethylarnino- 1 -butyne 1-chloro-3-phenyl-3 -n-butylamino-l -hexyne 1-chloro-3-phenyl-3-ethylaminol-nonyne 1-chloro-3-phenyl-3-t-butylamino-l-propyne 1-chloro-3 -allylamino-3-phenyll-butyne 1-bromo-3-phenyl-3-cyclohexylaminol-butyne 1-chloro-3-a1nino-3-phenyl-l-butyne l-bromo-3-ethylamino-3 -,8-naphthyl-1-butyne 1-chloro-3-ethylamino3-phenyl-3-a-thienylpropyne and the like.

The free bases of this invention are oils or low melting solids while their acid addition salts are generally white crystalline solids. The free bases are preferably prepared according to the following equation:

( (III) wherein R, R R R and Hal have the same significance as hereinabove. According to the equation, an acetylenic amine (I) is reacted with an alkali-metal base such as sodamide or potassium amide to form the corresponding alkali-metal salt of the acetylene (II). This alkali-metal salt is, in turn, reacted with an arylsulfonyl halide such as p-tosyl chloride or p-tosyl bromide to yield the corre sponding amino halo-acetylene (111). Other halogenating agents, in particular those which contain a positive halogen'such as N-bromsuccinimide and the hypohalous acids, can be used in place of the arylsulfonyl halide in the above syntheisis to prepare the compounds of this invention.

The acetylenic amines (I) which are starting materials for the above syntheses can be prepared in a number of ways depending upon the character of the constituent groups R, R R and R For example when'R and R are hydrogen and R and R are aliphatic, the method of Hennion and Teach, J. Am. Chem. Soc., 75, 1653 (1953), will furnish the desired primary acetylenic amine. When all of R, R R and R are aliphatic, the compounds can be prepared by the method of Hennion and Nelson, J. Am. Chem. Soc., 79, 2142 (1947). On the other hand, when any of R, R R and R is an aromatic radical, the method disclosed in the co-pending application of Nelson R. Easton and George F. Hennion, Serial No. 138,591, filed September 18, 1961, or the method disclosed in the co-pending application of Nelson R. Easton and Robert D. Dillard, Serial No. 138,585, filed September 18, 1961, can be employed to provide the desired starting material.

The acid addition salts of the amino haloacetylenes of this invention are readily prepared by methods fully set forth in the prior art. For example, it a solid acid is to be employed in forming the acid addition salt, and equivalent of this acid, either as a solid or in solution, is added to a solution containing an equivalent of the aminoacetylen. If the acid addition salt thus formed is insoluble in the reaction solvent, the salt is isolated by filtration or centrifugation. On the other hand, if the salt is soluble in the reaction medium, it can be isolated as a solid residue by evaporation of the volatile constituents. When a gaseous acid, as for example hydrogen chloride, is employed, it is possible to use an excess of the acid since the excess can be readily removed by volatilization.

Among the acids which form acid addition salts with the amines of this invention are inorganic acids including hydrochloric acid, hydrobromic acid, hydriodic acid, sulphuric acid, phosphoric acid, nitric acid, and the like, as well as organic acids, including acetic acid, tartaric acid, benzoic acid, naphthylensulfonic acid, p-toluenesulfonic acid, succinic acid, maleic acid, 2,4-dinitrobenzoic acid. and the like.

The compounds of this invention are useful as chemical intermediates, since they contain two readily modifiable groupsthe acetylenic bond and the reactive halo en atom. For example, the acetylenic bond can be hydrated to yield a ketone and the halogen atom can be hydrolyzed to yield a hydroxy group, thus giving a ketol grouping adjacent to an amine function. The keto group of the ke-tol can also be reduced, to form an amino 1,2glycol. In the same Way, the acetylenic bond can be hydrogenated to give a haloethylene derivative, hydration of which type of compound yields an whale-alcohol containing an amine group beta to the alcohol group. The acetylenic bond can also be hydrogenated past the ethylenic bond stage to give a saturated ut-halo-amine, which compound can be cyclized directly to yield an azetidine. Similarly, the a-haloketone produced by the hydration of the acetylenic bond can be cyclized to yield an azetidinone. Both the azetidines and azetidinones thus produced have useful pharmaceutical activity as for example as hypotensive agents or as sympatholytic agents. The acid addition salts of the amine bases represented by the above formula can be used interchangeably with the base itself in various processes. In addition the acid addition salts are useful in isolating and purifying the amine bases themselves.

The above examples of the utilization of the amino haloacetylene of this invention as intermediates are for the purposes of illustrations only, and it will be apparent to those skilled in the art that many other types of compounds can be prepared by operating upon the acetylenic bond, the acetylenic halogen, or the amine function singly or in combination by processes already illustrated in the prior art, such processes including hydrogenation, hydration hydrolysis, substitution, and the like.

A preferred group of compounds represented by the above formula are those in which R and R represent lower alkyl groups, as for example methyl, ethyl or isopropyl, or when taken together with the carbon atoms to which they are attached represent a cyclohexane ring; in which R represents a lower alkyl group such as ethyl, isopropyl, t-butyl or t-amyl; in which R is either hydrogen or methyl and Hal is chlorine or'bromine. These compounds have a very desirable pharmaceutical activity in that they afiect the central nervous system in desirable ways. Some of the compounds are potent hypotensive agents whereas others are stimulant amines. Compounds which demonstrate hypotensive action include 1-chloro-3- t-butylamino-3-methyl-l-butyne, 1-bromo-3-t-butylamino- 3-methyl-1-butyne, N-methyl-N-t-butyl-l-bromo-3-amino- 3-methyl-1-butyne, and l-t-butylamino-l-bromethynylcyclohexane. 1-chloro-3-t-butylamino-3-methyl-1-heptyne is an extremely potent sympathomimetic agent.

This invention is further illustrated by the following specific examples.

EXAMPLE 1 Preparation of 1-chI0r0-3-t-butylamino-3-methyl-1-butyne A suspension of sodamide in liquid ammonia was prepared by adding 2.59 g. of sodium in small pieces to about 300 ml. of liquid ammonia in the presence of a catalytic quantity of iron chloride. 13.99 g. of 3-t-butylamino-3'- methyll-butyne were added to the sodamide suspension in dropwise fashion, thus forming the sodium salt of the acetylen. The reaction mixture was stirred for about one hour at the end of which time 250 ml. of anhydrous ether Were added. The reaction mixture was next heated to refluxing temperature for about one hour, thus expelling all of the ammonia and leaving an ethereal suspension of the sodium salt of the acetylene. A solution of g. of p-tosyl chloride in 150 ml. of anhydrous ether was added; the resulting mixture was stirred for about two hours and was then allowed to remain at ambient room temperature over night. 200 m1. of water were added to the reaction mixture; the ether layer was separated and dried, and the ether was removed by evaporation in vacuo, leaving as a residue 1-chloro-3-t-butylamino-3-methyl 1 butyne formed in the above reaction. Distillation of the residue through a spinning-band fractionating column yielded purified 1-chloro-3-t-butylamino-3-methyl-l-butyne boiling at about 55 C. at a pressure of about 10 mm. of Hg; 12 1.451.

1-chloro-3-t-butylamino-3-methyl-l-butyne as prepared above was dissolved in anhydrous ether and an excess of an alcoholic hydrogen chloride solution was added to the ethereal solution, thus forming 1-chloro-3-t-butylamino-3- B-methyl-l-butyne hydrochloride which was isolated by filtration and which melted at about 158-9 C. after recrystallization from ethyl acetate.

Analysis.-Calc.: C, 51.43; H, 8.16; N, 6.67. Found: C, 51.93; H, 8.11; N, 6.41.

The following compounds were prepared by chlorinating or brominating the corresponding amino acetylene according to the procedure of Example 1. Their hydrochloride salts were formed as set forth in the same example.

l-chloro-3-t-amylamino-3-methyl-l-butyne. B.P. 55/4 mm. Hg; n =1.455. Hydrochloride salt: M.P. 1234 C. Analysis.-Calc.: Cl, 31.63; N, 6.25. Found: Cl, 31.63; N, 5.97.

1-chloro-3-isopropylamino-3,4-dimethyl-l-pentyne. B.P 53 C./ 5 rmn. Hg; n =1.452. Hydrochloride salt: M.P. 174-6 C. Analysis.--Calc Cl, 31.63; N, 6.25. Found: Cl, 31.39; N, 5.99.

1-chloro-3-t-butylamiuo-3-methyl-l-heptyne. B.P. 83 C./5 mm. Hg; n =1.456. Hydrochloride salt: M.P. 122-4 C. Analysis.-Calc.: Cl, 28.11; N. 5.55. Found: Cl, 28.31; N, 5.45.

l-ethylamino-l-chlorethynylcyclohexane. B.P. 47-51 C./1 mm. Hg; Hydrochloride salt M.P. 2l0-12 C. Analysis.Calc.: Cl, 15.96; N, 6.31. Found: Cl, 16.22; N, 6.20.

N-methyl-N-t-butylamino-1-bromo-3-amino-3-methyl-1- butyne. B.P. 495l C./ 1 mm. Hg; n =1.490. Hydrochloride salt: M.P. 242 C. Analysis.-Calc.: C, 44.70; H, 7.13; N, 5.22. Found: C, 44.78; H, 7.10; N, 5.28.

l-bromo-3-isopropylamino-3-methyl-l-butyne. Hydrochloride salt: M.P. 212214 C. Analysis.Calc.: C, 42.45; H, 6.73; N, 5.50. Found: C, 42.64; H, 6.74; N, 5.71.

1-bromo-3-ethylamino-3-ethyl-l-pentyne: low melting solid which sublimes upon distillation. Hydrochloride salt: M.P. 2l9-2-0 C. Analysis.Calc.: C, 39.94; H, 6.28; N, 5.82. Found: C, 39.97; H, 6.50; N, 5.54.

1-ehloro-3-ethylamino-3-phenyl-l-butyne. B.P. 8894 C./4 mm Hg. Hydrochloride salt: M.P. 1535 C. Analysis.Calc.: C, 59.03; H, 6.19. Found: C, 59.05; H, 6.33.

EXAMPLE 2 Preparation of N-methyl-N-ethyl-I-br0m0-3- amino-3-methyl-1 -butyne About 4 g. of sodium were added in small pieces to 300 ml. of liquid ammonia in the presence of a catalytic quantity of iron chloride, thus forming a suspension of sodamide in liquid ammonia. About 13.2 g. of N-methyl- N-ethyl-3-amino3-methyl-l-butyne hydrochloride were added to the sodamide suspension, thus forming the sodium salt of the acetylene with sodium chloride as a byproduct. After stirring the liquid ammonia reaction mixture for one hour, 400 ml. of ether were added and the reaction mixture was allowed to warm up to ambient room temperature, during which period a major part of the ammonia had evaporated. The ethereal reaction mixture was then heated to refluxing temperature for about one hour to expel the last traces of ammonia. A solution of 19.5 g. of p-tosyl bromide in 200 ml. of anhydrous ether was added to the suspension of the sodium salt of the acetylene, thus forming N-methyl-N-etliyl l bromo-3- amino-3-methyll-butyne. Afterlthe addition of the ptosyl bromide had been completed, the reaction mixture was stirred at refluxing temperature for about one hour and was then cooled. 200 ml. of water were added. The ethereal layer was separated and was extracted with ml. of l N hydrochloric acid, thus causing N-methyl-N- ethyl-l-bromo-3-amino-3-methyl-1-butyne to pass into the aqueous acidic layer as the hydrochloride salt. The aqueous acidic layer was made basic by the addition of an excess of 50 percent (w./v.) sodium hydroxide, thus forming N methyl N-ethyl-l-bromo-3-amino-3-methy1-lbutyne free base. The free base was insoluble in the basic aqueous layer and was extracted into ether. The ethereal layer was separated and dried, and the ether was removed by evaporation in vacuo, leaving N-methyl-N-ethyl-lbromo-3-amino-3-methyl-l-butyne as a crystalline residue.

N methyl N ethyl-1-bromo-3-amino-3-methyl-1- butyne, thus prepared was dissolved in 50 ml. of ethanol. An excess of ethanolic hydrogen chloride was added, thus forming N methyl-N-ethyl-l-bromo-3-methyl-l-butyne hydrochloride, which melted at about 196-7 C. after recrystallization from an. ethanol-ether solvent mixture.

Analysis.-Calc.: N, 5.82; Found: N, 5.53.

The following compounds were prepared by halogenating the corresponding amino acetylene hydrochloride salt as set forth in the above example.

3-amino-1-bromo-3-isopropyl4-methyl 1 pentyne. B.P. 48 C./1 mm. Hg. Hydrochloride salt: sublimed at 225 C. Analysis.-Calc.: C, 42.45; H, 6.73; N, 5.50. Found: C, 42.60; H, 6.62; N, 5.62.

1 ethylamino-1-bromo-ethynylcyclohexane. Hydrochloride salt: M.P. 248 C. Analysis.Calc.: C, 45.04; H, 6.43; N, 5.25. Found: C, 45.56; H, 6.61; N, 5.10.

l-(t-butylamino)-1-chlorethynylcyclohexane. B.P. 61 C./1 mm. Hg; m =1.485. Hydrochloride salt: M.P. 208-10 C. Analysis.Calc.: N, 5.60; Cl, 28.34. Found: N, 5.80; Cl, 28.19.

1-(3-t-butylamino)-1-bromo-ethyny1 cyclohexane. Hydrochloride salt: M.P. 241-2 C. with decomposition. Analysis-Calc.: C, 48.91; H, 7.18; N, 4.75. Found: C, 49.06; H, 7.32; N, 4.81.

EXAMPLE 3 Preparation of 1-br0mo-3-t-buty[amino-.i-methyl- -butyne 27.8 g. of 3-butylamino-3-methyl-l-butyne and 35.8 g. of N-bromosuccinimide were mixed with 250 ml. of carbon tetrachloride. The reaction mixture was heated to refluxing temperature for about fourteen hours, at the end of which time it was cooled and filtered. The carbon tetrachloride was removed by evaporation in vacuo, leaving as a residue 1 -'bromo 3 t butylamino-3-methyl-1- butyne formed in the above reaction. The compound was purified by distillation, and boiled in the range 50-60 C. at a pressure of about 0.5 mm. Hg.

1-bromo-3-t-butylamino-3-methyl-l-butyne prepared as above was dissolved in ethyl acetate and the resulting solution was saturated with gaseous hydrogen chloride, thus forming 1-bromo-3-t-butylamino-3-methyl-l-butyne hydrochloride, which melted at about =183-5 C. after recrystallization from methyl ethyl ketone. Analysis. Calc.: C, 42.45; H, 6.73. Found: C, 42.04; H, 6.82.

We claim:

1. A compound selected from the group consisting of the amino-haloacetylenes represented by the following formula and the acid addition salts thereof:

R-JJ-CEC-Hal wherein R and R when taken separately, are members of the group consisting of hydrogen, (l -C alkyl, C C alkenyl, lower alkoXy-substituted C -C alkyl, lower alkoxy-substituted C -C alkenyl, cycloalkyl, cycloalkenyl monocyclic and bicyclic aryl, and substituted monocyclic and bicyclic aryl wherein said aryl substituents are members of the group consisting of chlorine, bromine, C -C alkyl, C -C alkenyl, nitro, perfiuoro lower alkyl, perchlorolower alkyl, acetamido, lower alkoXy, and di-lower-alkylamino, and, when taken together with the carbon atom to which they are attached, form a member of the group consisting of cycloalkyl, cycloalkenyl, and monocyclic and bicyclic aryl; R and R when taken separately, are members of the group consisting of hydrogen, C -C alkyl, C C alkenyl, cycloalkyl, cycloalkenyl, monocyclic and bicyclic aryl, substituted monocyclic and bicyclic aryl wherein said aryl substitutents are members of the group consisting of chlorine, bromine, C -C alkyl, C C alkenyl, nitro, perfiuoro lower alkyl, perchloro lower alkyl, acetamido, lower alkoxy, di-loweralkylamino, and monocyclic aryl-substituted lower alkyl, and when taken together with the nitrogen atom to which they are attached, form a member of the group consisting of morpholino, thiomorpholino, piperidino, pyrrolidino, and 4-lower alkylpiperazino; and Hal is a halogen atom of atomic number greater than 10.

8 2. A compound represented by the formula all;

Am- -0EG-X all;

References Cited in the file of this patent UNITED STATES PATENTS 2,613,208 Van Hook et al Oct. 7, 1952 2,665,311 McKeever et a1 Jan. 5, 1954 2,901,886 Doerner Sept. 1, 1959 3,007,933 Hennion Nov. 7, 1961 3,067,101 Easton et a1. Dec. 4, 1962 OTHER REFERENCES Truchet: Ann. de Chim., 10th Series, vol. 16, pp. 309- 33s 1931 Marszak-Fleury: Ann. Chim. (Paris), Series 13, vol. 3, pages 656-7l 1 (1958).

Dobson et al.: J. Chem. Soc. (London), volume of 1958, pages 36423647. 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF THE AMINO-HALOACETYLENES REPRESENTED BY THE FOLLOWING FORMULA AND THE ACID ADDITION SALTS THEREOF: 